PARALLEL DNA CONTAINING PYRAZOLO[3,4-D]PYRIMIDINE ANALOGUES OF ISOGUANINE

The phosphoramidites of 8-aza-7-deaza-2′-deoxyisoguanosine (1a) and its bromo derivative 1b as well as of 6-aza-2′-deoxyisocytidine and its 5-methyl derivative (3a,b) were synthesized. Parallel-stranded duplexes containing the nucleosides 1a,b show a significantly enhanced duplex stability compared to those containing 2′-deoxyisoguanosine.     

Synthesis of Oligodeoxynucleotides Containing 4′-C-Aminoalkyl-thymidines and Their Thermal Stability and Nuclease-Resistance Properties

Abstract

To find the nuclease-resistant oligodeoxynucleotides (ODNs) with natural phosphodiester linkages, we designed and synthesized ODNs containing 4′-C-aminoalkylthymidines (1–4). We found that the ODNs containing 1, 2, 3 or 4 were more resistant to nucleolytic hydrolysis by both snake venom phosphodiesterase (a 3′-exonuclease) and DNase I (an endonuclease) than unmodified ODNs.     

Synthesis of a Cyclopentane Amide DNA Analogue and Its Base Pairing Properties

Abstract

cpa-DNA monomers containing the bases adenine and thymine have been synthesized starting from the known compound 1 in 12 steps. Partially and fully modified cpa-thymidine and cpa-adenosine containing oligodeoxynucleotides were synthesized by standard oligonucleotide chemistry. Fully modified homo-cpa-A sequences lead to duplex destabilization by ?1.4°C/mod. relative to DNA. As its congener bca-DNA, cpa-DNA prefers left-handed duplex formation where possible.     

Elucidation of the Hydrolytical Properties of α-Hydroxybenzylphosphonates as a New Potential Pro-Oligonucleotide Concept

Abstract

The synthesis of Fpmp-protected α-hydroxybenzylphosphonate modified oligonucleotides as potential new pro-oligonucleotides is described. The proposed hydrolytic pathways of the oligonucleotides were studied using two dimers 2 and 4 and the tetramer 6 containing one α-hydroxybenzyl modification as model compounds.     

Exosomes-delivered PD-L1 siRNA and CTLA-4 siRNA protect against growth and tumor immune escape in colorectal cancer

ObjectiveThis study aims to dissect impacts of exosomes-delivered PD-L1 and CTLA-4 siRNAs on colorectal cancer (CRC) progression and immune responses.MethodsExosomes containing PD-L1 siRNA and CTLA-4 siRNA were prepared and utilized to treat CRC cells to evaluate their effects. A tumor-bearing mouse model was established for verification.ResultsExosomes containing PD-L1 siRNA and CTLA-4 siRNA repressed malignant features of CRC cells and restrained tumor growth and activated tumor immune responses in vivo. Co-culture of CRC cells treated with exosomes containing PD-L1 siRNA and CTLA-4 siRNA with human CD8⁺ T cells increased the percentage of CD8⁺ T cells, decreased the apoptotic rate of CD8⁺ T cells, elevated IL-2, IFN-γ, and TNF-α expression in cell supernatants, reduced adherent density of CRC cells, augmented the positive rate of CRC cells, and subdued tumor immune escape.ConclusionExosomes containing PD-L1 siRNA and CTLA-4 siRNA suppressed CRC progression and enhanced tumor immune responses.     

具ACC脱氨酶活性大豆根瘤内生菌的筛选、抗性及促生作用北大核心CSCD

【目的】从大豆根瘤中筛选具ACC(1-氨基环丙烷-1-羧基)脱氨酶活性的内生细菌,对活性菌株的抗盐碱性、系统分类地位以及代表菌株的促生长作用进行研究,为发掘和应用抗逆、促生优良菌种资源提供理论基础。【方法】以ACC作为唯一氮源测定菌株产ACC脱氨酶特性,采用标准曲线法测定α-丁酮酸含量,比色法定量测定ACC脱氨酶活力,固体平板筛选法对活性菌株进行抗性分析,通过菌体形态及生理生化特性测定、16S rRNA基因序列同源性分析鉴定菌株分类地位,采用盆栽试验验证代表菌株的促生作用。【结果】从河南省13个市(地区)36个点采集的大豆根瘤中筛选出8株ACC脱氨酶内生细菌,其中菌株DD132的酶活性最高(15.712 U/mg)。筛选菌株可耐受4%–6%NaCl,其中菌株DD165、DD132可耐受9%NaCl盐浓度。在pH 11时5株(DD14、DD132、DD67、DD141、DD131)生长良好,说明这些菌株有较强耐碱性。8株产ACC脱氨酶菌株分属于4属,即芽孢杆菌属(Bacillus)、肠杆菌属(Enterobacter)、寡养单胞菌属(Stenotrophomonas)和泛菌属(Pantoea)。接种试验表明内生菌DD132对小麦幼苗生长具有明显促生长作用。【结论】大豆根瘤内具ACC脱氨酶高活性菌株有较强耐盐碱性,其中菌株DD132对小麦幼苗生长有明显促生长作用。为发掘和应用抗逆、促生的优良菌种资源提供理论基础。     

A BUNCH-OLIGONUCLEOTIDE FORMING STABLE MONOMOLECULAR QUADRUPLEX CONTAINING A T-TETRAD

The chemical synthesis of bunch-ODN I and II prone to form quadruplex structures containing G-and T-tetrads has been reported. Structural studies were performed by ¹H-NMR and CD melting experiments.     

Amino Acid Nucleic Acids: Synthesis and Hybridization Properties of a Novel Class of Antisense Oligonucleotides

Abstract

Oligonucleotides containing novel phoshoramidite 12 were synthesized and studied for their hybridization properties for the first time. Interestingly, these modified oligonucleotides showed a remarkable resistance to exonuclease.     

Synthesis and Nuclease Stability of Dinucleotides Containing an Anti- conformationally Constrained Acyclic Thymidine

Abstract

Novel heterodimers containing an anti conformationally constrained acyclic thymidine were prepared and the nuclease resistance of the modified dinucleotides were studied.     

Dimeric Oligonucleotide Synthons Containing 2-Deoxy-3-O-Phosphonomethyl-α-D-erythro-pentofuranosyl Nucleosides

Abstract

The synthesis of 2′-deoxy-3′-O-phosphonomethyl-α-D-erythro-pentofuranosyl-thymine and -adenine (1, B is Thy or Ade) is described. Dimeric oligonucleotide synthons such as 2 containing isosteric phosphonate internucleoside linkage were prepared.     

Nucleosides and Nucleotides. 165. Chemical Ligation of Oligodeoxynucleotides Having a Mercapto Group at the 5-Position Of 2′-Deoxyuridine via a Disulfide Bond #

Abstract

We describe the nonenzymatic ligation of oligodeoxynucleotides (ODNs) containing a mercapto group at the 5-position of 2′-deoxyuridine via a disulfide bond. Two ODNs containing different sequences were efficiently ligated in the presence of a template by this method.

     

Fluorinated Peptide Nucleic Acid

Abstract

The fluorinated olefinic peptide nucleic acid analogue (F-OPA) monomer containing the base thymine was synthesised in 13 steps. PNAs containing this unit were prepared and their pairing properties assessed by means of UV-melting experiments.     

Oligomerization Aiming at Phosphonate Analogues of Oligoadenylates

Abstract

This work deals with isopolar, phosphonate-based nucleotide analogues containing a bridging P-C bond instead of the ester P-O linkage. Specifically, starting from activated derivatives 1, 2, and 3, a simple process for preparation of mixtures of short oligomers and their analyses were elaborated.     

Synthesis and Hybridization Properties of Oligonucleotides Containing (2 S ,3 R )-9-(2,3,4-Trihydroxybutyl)Adenine

The synthesis and properties of oligonucleotides (ONs) containing 9-(2,3,4-trihydroxybutyl)adenine, A ^C2 and A ^C3, are described. The ON containing A ^C2 involves the 3′ → 4′ and 3′ → 5′ phosphodiester linkages in the strand, whereas that containing A ^C3 possesses the 3′ → 4′ and 2′ → 5′ phosphodiester linkages. It was found that incorporation of the analogs, A ^C2 or A ^C3, into ONs significantly reduces the thermal and thermodynamic stabilities of the ON/DNA duplexes, but does not largely decrease the thermal and thermodynamic stabilities of the ON/RNA duplexes as compared with the case of the ON/DNA duplexes. It was revealed that the base recognition ability of A ^C2 is greater than that of A ^C3 in the ON/RNA duplexes.     

Discovery and Evaluation of Terephthalic Acid Derivatives as Potent α4β1 Integrin Antagonists

Terephthalic acid based derivatives containing β- and γ-amino acid residues were prepared as antagonists of the leukocyte cell adhesion process that is mediated through the interaction of the very late antigen 4 (VLA-4) and the vascular cell adhesion molecule 1 (VCAM-1). The compounds 2, 10–12, 14, and 16–17 inhibited the adhesion in a cell based assay in the low and sub micromolar range.     

Quinazoline-sulfonamides as potential antitumor agents: synthesis and biological testing

Abstract

New series of quinazoline containing sulfonamide derivatives were prepared and screened for their antitumor activity. Four human cancer cell lines, namely, hepatoma cancer cell line (HepG2), breast cancer cell line (MCF-7), cervix cancer cell line (HeLa) and colon cancer cell line (HCT-8), were used to measure the cytotoxic activity. Compounds 8 and 21 exhibited remarkable antitumor activity almost similar to that of the standard drug (doxorubicin). Six compounds 16, 22, 23, 29, 30 and 33, showed considerable activity and few compounds were totally inactive.     

Structure-activity relationships of alkaloids from mesquite (<Emphasis Type="Italic">Prosopis juliflora</Emphasis> (Sw.) DC.)

The structure–activity relationships of alkaloids (1–5) from mesquite were subjected to assessment of growth inhibition against the shoot and root growth of monocotyledonous plants, barnyard grass, rice and timothy, and dicotyledonous ones, amaranth, lettuce and cress. All alkaloids tested generally showed growth inhibitory against both monocotyledonous and dicotyledonous plants. Furthermore, these alkaloids exhibited higher activity against the growth of root than that of shoot of all plant species used, except that juliprosopine (5) showed higher activity against the shoot growth than the root growth of rice seedling. Among these alkaloids, the highest active compound appeared to be juliprosine (4), followed by a (1:1) mixture of 3-oxo- and 3-oxo-juliprosine (3a and 3b), and juliprosopine (5). The activity of juliprosine (4) containing 2-methyl piperidine bearing hydroxyl groups at C-3 and C-3 was higher than that of 3-oxo- and 3-oxo-juliprosine (3a and 3b) containing 3-oxo- and 3-oxo-2-methylpiperidine. Compound 3 and 4 containing dihydroindolizinium ring showed higher activity than compound 5 containing tetrahydroindolizine ring, whereas compound 1 containing tetrahydroindolizinone ring showed weaker activity. The activity of secojuliprosopinal (2) without indolizine ring was very weak. It was thus clarified that the active sites in the chemical structure of alkaloids from mesquite are the functional group at C-3 and C-3 of piperidine and indolizine skeleton.     

Analogues of both Leu- and Met-enkephalin containing a constrained dipeptide isostere prepared from a Baylis-Hillman adduct

An efficient route was developed for the synthesis of the Fmoc-protected dipeptide 4, isostere of Gly-Gly containing an α-methylene β-amino acid; the conformationally restricted analogues of Leu-enkephalin, 3a, and Met-enkephalin, 3b, respectively, were prepared by changing 4 for Gly²-Gly³ in the native compounds 3a and 3b whose biological activities were significantly lower than the parent compounds.     

Synthesis of 3,4-dihydroxypyrrolidine-2,5-dione and 3,5-dihydroxybenzoic acid derivatives and evaluation of the carbonic anhydrase I and II inhibition

Abstract

The inhibition of two human cytosolic carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I and II, with some 3,4-dihydroxypyrrolidine-2,5-dione and 3,5-dihydroxybenzoic acid derivatives, were investigated by using the esterase assay, with 4-nitrophenyl acetate (4-NPA) as substrate. Compounds 10–13 showed K_I values in the range of 112.7–441.5?μM for hCA I and of 3.5–10.76?μM against hCA II, respectively. These hydroxyl group containing compounds generally were competitive inhibitors. Some hydroxyl group containing compounds investigated here showed effective hCA II inhibitory effects, in the same range as the clinically used sulfonamide acetazolamide, and might be used as leads for generating enzyme inhibitors possibly targeting other CA isoforms which have not been yet assayed for their interactions with such agents.     

Properties of Oligonucleotides Containing the Transition Bases P and K

Abstract

The properties of the degenerate nucleosides dP and dK, in templates and primers were determined. dP was copied as either pyrimidine, dK as either purine. In primers, an equimolar mixture of the two nucleosides functioned as a universal base equivalent in both sequencing and the polymerase chain reactions. Cloning of DNA containing dP or dK produced transition mutations in vivo.